It is well known that individual cells, even those identical in appearance, differ in numerous characteristics, such as variability in the expression of a particular gene, concentration of a critical metabolite or ion, or pattern of response to a given stimulus. Living cells possess very low copy numbers of many components, including deoxyribonucleic acid (DNA) and important regulatory molecules. Both stochastic events inherent in the biochemical process of gene expression (intrinsic noise) and fluctuations in other cellular components (extrinsic noise) contribute substantially to overall variation among cells. Cell types, mutations, and fluctuations all contribute to the diversity of cells in the body.
However, most clinical or cell-based assays analyze cells in bulk, using serum or cell culture media. These assays often average the information over the whole cell population and do not provide detailed information that is critical to evaluate the state of biological system, such as 1) whether two or more genes are co-expressed in the same cell or in different sub-populations of the cells; 2) whether a small increase in expression measured in the ensemble results from a small, homogeneous increase across all cells or a large increase in a subset of cells.